Beyond MS, Cannabis Unproven in Neurology

by John Gever John Gever,Deputy Managing Editor, MedPage Today
April 28, 2014

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Action Points

Note that this meta-analysis demonstrated that there is insufficient evidence of efficacy for medical cannabis treatment for most neurological conditions, save multiple sclerosis.

Be aware that legislative barriers to clinical trials involving cannabis have limited progress in this field to some extent.

PHILADELPHIA -- Marijuana has no proven benefit for any neurological disorder other than multiple sclerosis (MS) but does have significant adverse effects, an American Academy of Neurology evidence review found.

For the most part, the lack of documented efficacy is because cannabis has not yet been tested rigorously -- or at all -- as therapy for such conditions, according to the review by Barbara Koppel, MD, of New York Medical College in New York City, and other members of the AAN's guideline development panel.

The review was published in the AAN's flagship journal Neurology in conjunction with the group's annual meeting here. It was also endorsed by the American Epilepsy Society, the American Autonomic Society, and the International Rett Syndrome Foundation.

At an AAN press conference, Koppel observed that marijuana is seldom prescribed, "but it may be overused -- people are still using it on their own."

She also noted that patients obtaining cannabis products from dispensaries where medical uses are legal don't typically get specific advice from their physicians, and hence the AAN review did not address it specifically.

She said the physician's role in those states is to certify that patients have a condition listed by the state as a qualification for medical marijuana treatment; detailed consultations on what specific product to buy is left to dispensary staff.

As such, "that's totally out of the purview of this review," Koppel said.

Added fellow panel member Gary Gronseth, MD, of the University of Kansas Medical Center in Kansas City, "When we say that there's insufficient information or insufficient evidence that [something] is effective for a condition, that's not the same thing as saying that there's evidence that it's not effective for that condition."

In March, the committee's findings on marijuana and associated products as treatments for various aspects of MS were published as a separate guideline. As is clear from the new review, the evidence base for those applications is much more extensive than for use in other conditions.

But in addition to applications in MS, the panel also examined several other conditions for which cannabis products have reportedly been used. Primarily these have been those marked by involuntary movements, including Huntington's disease, Tourette syndrome tics, cervical dystonia, and levodopa-triggered dyskinesias in Parkinson's disease. The committee also analyzed the evidence that cannabis products may reduce seizure frequency in epilepsy.

The potential use of cannabinoids for other conditions was not covered in the guideline because the panel found no evidence of any kind to review.

There was not much to analyze for any condition other than MS, it turned out.

Koppel and colleagues identified a single high-quality trial of the cannabis derivative nabilone for Huntington's disease, one study of cannabidiol for levodopa-related dyskinesia, and none for Tourette syndrome, cervical dystonia, or epilepsy. The panel did consider seven other studies of lesser quality.

On the other hand, Koppel and colleagues were persuaded that cannabis products have enough adverse effects to cause clinical concern, although this was not shown in rigorous studies.

Their meta-analysis of placebo-controlled studies involving a total of some 3,000 patients showed that three times as many treated with cannabinoids stopped because of adverse effects compared with controls. But those studies were mostly vague on the causes for discontinuations.

Nevertheless, Koppel and colleagues referred to other analyses "outside of treatment trials" that identified increases in cognitive impairment.

"Some patients who have neurological conditions may have preexisting cognitive dysfunction, which may increase their susceptibility to cannabinoids' toxicities," they wrote in the guideline.

Of particular concern was a report of four seizures in an MS trial conducted in Great Britain involving more than 600 patients, Koppel said at the press conference. Two were in patients with no previous seizure history, and the trial investigators indicated that they were at least possibly medication-related.

Suicidality has also been reported in trial data, the panel found. "It is especially concerning that a medication that may have an adverse effect of suicide may be prescribed in a population such as patients with MS who are already at increased suicide risk," they wrote.

Not surprisingly, the committee called for randomized trials to provide better evidence both for the possible utility of cannabis products for neurological conditions as well as for the risks.

"There's a place for it [medical marijuana in neurology] and more work is going to need to be done to figure out exactly where," said Koppel.

The work had no commercial funding. All guideline authors disclosed that they had no relevant relationships with industry.

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